Myriad Genetics and Personalis Partner to Market Solutions to Pharma Customers

Myriad expands pharma service offering by introducing Personalis’ ImmunoID NeXT® platform to its pharmaceutical partners who use MyRisk® Hereditary Cancer Test, BRACAnalysis CDx® and/or MyChoice® CDx cancer tests Myriad expands pharma service offering by introducing Personalis’ ImmunoID NeXT® platform to its pharmaceutical partners who use MyRisk® Hereditary Cancer Test, BRACAnalysis CDx® and/or MyChoice® CDx cancer tests

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Myriad Genetics and Personalis Partner to Market Solutions to Pharma Customers

GENFIT Highlights ACLF Development Strategy at “ACLF Day” during AASLD The Liver Meeting® 2023

Lille (France), Cambridge (Massachusetts, United States), Zurich (Switzerland), November 16, 2023 – GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with rare and life-threatening liver diseases, today announced the highlights from its “ACLF Day” held on November 11, 2023 during AASLD The Liver Meeting ® in Boston, MA (USA).

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GENFIT Highlights ACLF Development Strategy at “ACLF Day” during AASLD The Liver Meeting® 2023

Polaris Group Initiates Rolling Submission of Biologic License Application (BLA) for ADI-PEG 20 with U.S. FDA to Treat Malignant Pleural Mesothelioma

TAIPEI, Taiwan and SAN DIGEO, Nov. 16, 2023 (GLOBE NEWSWIRE) -- Polaris Group (The Company, TWSE:6550), today announced that the Company has initiated the rolling submission of its Biologic License Application (BLA) for ADI-PEG 20 to the U.S. Food and Drug Administration (FDA) for the systemic treatment of patients with malignant pleural mesothelioma with non-epithelioid histology, in combination with a platinum agent and pemetrexed. This submission is based on the results of the successful phase 3 trial of ADI-PEG 20 in combination with a platinum agent and pemetrexed which met both its primary and secondary objectives for progression free survival and overall survival. The rolling submission process allows for the submission of individual modules of the BLA as they are completed, which can streamline the regulatory review process and may expedite the potential approval timeline.

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Polaris Group Initiates Rolling Submission of Biologic License Application (BLA) for ADI-PEG 20 with U.S. FDA to Treat Malignant Pleural Mesothelioma

Verona Pharma’s President and CEO David Zaccardelli Wins Executive of the Year SCRIP Award

LONDON and RALEIGH, N.C., Nov. 17, 2023 (GLOBE NEWSWIRE) -- Verona Pharma plc (Nasdaq: VRNA) (“Verona Pharma” or the “Company”), announces its President and CEO, David Zaccardelli, has won ‘Executive of the Year 2023’ at the SCRIP Awards in recognition of his exemplary leadership.

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Verona Pharma’s President and CEO David Zaccardelli Wins Executive of the Year SCRIP Award

Healing of acute anterior cruciate ligament rupture on MRI and … – British Journal of Sports Medicine

Background

A common belief among researchers and clinicians is that a ruptured anterior cruciate ligament (ACL) has limited healing capacity. This belief has shaped current management strategies for ACL rupture. However, anatomical studies have demonstrated that the ACL has a rich vascular supply1 2 and histological studies describe ruptured ACLs passing though the typical phases of healing after injury, despite a slower rate of healing and reduced healing capacity compared with medial collateral ligament rupture.35 An absence of tissue bridging the gap between ligament remnants has been observed, which may inhibit healing of ACL rupture.6 The distance between the ACL origin to its insertion is shortest at 90135 of knee flexion.7 We have developed the novel Cross Bracing Protocol (CBP) that aims to reduce the gap distance between the ligament remnants by immobilising the knee at 90 of flexion for 4 weeks after acute ACL rupture in attempt to facilitate bridging of tissue and healing between the ruptured ACL remnants. After 4 weeks, knee range-of-motion is increased at weekly increments and the CBP is coupled with physiotherapist-supervised rehabilitation targeting lower limb neuromuscular control, muscle strengthening and power, and functional training to enable return-to-sport and recreational activities.

A 2021 systematic review identified only six studies that evaluated ACL healing on MRI after ACL rupture.8 Studies were of low methodological quality and five studies included 50 participants.8 More recently, an analysis of the KANON Trial observed MRI evidence of ACL healing at a 2-year follow-up in 30% of participants who were randomised to initial rehabilitation and optional delayed ACL reconstruction (ACLR).9 Those with MRI evidence of ACL healing reported better 2-year knee function and quality of life (QOL), compared with participants with no MRI evidence of ACL healing, and participants managed with early or delayed ACLR.9 Many ACL injured people experience poor long-term outcomes, including sport and activity limitations, persistent pain, an early onset of osteoarthritis and poor long-term QOL.1013 Considering the suboptimal outcomes with current management strategies, and the potential for ACL healing to result in favourable outcomes, new strategies to preserve and heal the native ACL should be explored. The objective of this study was to investigate MRI evidence of ACL healing, patient-reported outcomes and knee laxity in the first 80 individuals with acute ACL rupture managed non-surgically with the CBP.

This case series investigates outcomes from 80 consecutive patients with acute ACL rupture who were managed with the CBP. Data were collected in the course of clinical practice, and all participants provided informed consent for their data to be included in this study.

Eighty patients between the ages of 10 years and 58 years (mean (SD): 26 years (10 years)), who presented to a private sport and exercise medicine physician in Sydney, Australia (TC), with MRI confirmed acute ACL rupture between March 2016 and September 2021, were managed with the CBP (figure 1). Twelve out of 80 patients were residing outside of Sydney or impacted by COVID-19 restrictions and underwent virtual specialist consultations (TC), supplemented by in-person management and assessment from an experienced sports and exercise physician and physiotherapists trained in the CBP.

Participant flow chart. ACL, anterior cruciate ligament; ACLR, anterior cruciate ligament reconstruction; CBP, Cross Bracing Protocol; DVT, deep vein thrombosis; MCL, medial collateral ligament.

Patients of all ages, were considered eligible for the CBP if they presented within 1 month of acute ACL rupture, confirmed on MRI (ie, an ACL OsteoArthritis Score (ACLOAS) grade 3 representing full discontinuity of the ACL). To be considered for the CBP, patients needed to be functionally independent and capable of managing a period of knee immobilisation. Patients were considered ineligible if they had clinical or MRI evidence of structural concomitant injuries that necessitated surgical intervention (eg, an unstable bucket-handle meniscal tear) or a history of deep vein thrombosis (DVT) or pulmonary embolism. After the 10th participant, DVT screening was added to the eligibility criteria, whereby all patients underwent Doppler ultrasound to exclude DVT. The flow of participants through the study, including reasons for not offering the CBP and reasons for choosing ACLR (no participants chose rehabilitation alone), is presented in figure 1.

Patients were informed about treatment options: early ACLR, non-operative rehabilitation with optional delayed ACLR or trialling the CBP. Patients received information on the rationale and theoretical justification for the CBP, and they were aware that this was an experimental treatment with a chance of failure and possible need for ACLR in the future. The decision to trial the CBP was based on patient preference.

The CBP and accompanying rehabilitation protocol is described in online supplemental appendix 1. In patients presenting in the first week post-injury, the use of cryotherapy and anti-inflammatory medications was discouraged to minimise impairment of the acute inflammatory response.5 14 Paracetamol was prescribed as needed for pain. Fourteen patients who presented 7 days post-injury with minimal or no hemarthrosis/effusion underwent a platelet-rich plasma injection.

The injured knee was then secured at 90 flexion in a standard limited range-of-motion brace as early as convenient following injury (range: 031 days post-injury, median (IQR): 5 days (411 days)), by a physiotherapist trained in the CBP. Patients were advised to keep the knee fixed in the brace at all times for the first 4 weeks, including during sleep and showering. Patients were educated regarding safe use of crutches during the first 8 weeks (and use of additional mobility aids if desired, such as a knee scooter, i-Walker or wheelchair), while unable to sufficiently extend the knee to walk unaided. Patients were given advice regarding self-care, comfort and DVT risk mitigation strategies, including hydration and calf pump exercises. Prophylactic Clexane injections were introduced after the 10th patient. From patient 20 onwards, Rivaroxiban 10 mg was prescribed (for the first 8 weeks of the CBP) instead of Clexane.

After 4 weeks, the range-of-motion brace was adjusted at regular increments to allow progressive increases in range-of-motion (see online supplemental appendix 1). At week 10, unrestricted range-of-motion was allowed, and the brace was removed at 12 weeks. Weight-bearing was encouraged within the available range and patients completed standardised goal-oriented exercise-based rehabilitation while in the brace, and after brace removal until the point of return-to-sport (online supplemental appendix 1). Patients had weekly physiotherapist consults to check/adjust the brace and progress exercise-based rehabilitation (online supplemental appendix 1). Return-to-sport was not recommended until 912 months post-injury, and was dependent on patient and clinical factors, including desire to return-to-sport, completion of required rehabilitation and passing functional return-to-sport criteria.15

The first 4 patients had the brace removed and their first follow-up assessment at 9 weeks. After this, a decision was made to extend the CBP from 9 weeks to 12 weeks to protect the ACL for longer and enable more accurate interpretation of the MRI at the time of brace removal. Additionally, two patients for personal reasons (work demands/to care for young children) removed the brace at the end of week 4 and week 6. Both patients were compliant with the CBP before brace removal and completed rehabilitation post brace removal.

Details of all outcomes, including measurement method, time of measurement and interpretation, are presented in table 1.

Outcome measurement and interpretation

Patients have been involved in the development and refinement of the CBP, and the authorship team includes a patient who was managed with the CBP (MD).

All patients with acute ACL rupture managed with the CBP prior to October 2021 participated in the study, including 31 (39%) females, people aged 1058 years at the time of injury, and both private (69%) and publicly (31%) funded patients. Although only 3 women are included in the authorship team, the lead researcher is a woman and we include authors from a variety of career stages and clinical disciplines.

All continuous variables were assessed for normality and mean (SD) or median (IQR) reported, as appropriate. Participant characteristics and outcomes are presented for all participants, and based on 3-month ACLOAS. Mann-Whitney U tests were used to compare continuous outcomes (Lysholm Scale and ACLQOL scores) and Pearsons 2 tests were used to compare categorical outcomes (Lachmans test, Pivot-shift test and return-to-sport) between groups with lower versus higher ACLOAS grades on 3-month MRI (ACLOAS grades 01 vs ACLOAS grades 23). Since seven participants completed the Lysholm Scale and ACLQOL score after ACL re-rupture, a subgroup analysis was performed to present data and compare groups after excluding these seven individuals from the analysis (online supplemental appendix 2). For the two participants with missing MRI data at 3-month follow-up (decided not to undergo MRI), the ACLOAS from 6-month MRI was used to classify 3-month ACLOAS for analysis (95% of participants had the same ACLOAS at 3 months and 6 months, only 1 participant had a worse ACLOAS grade due to re-injury). Six people were missing 6-month MRI data (due to ACL re-rupture (n=3), pregnancy (n=1) or decided not to undergo MRI (n=2)). Since only one participant had missing data for the Lysholm Scale and ACLQOL scores, a complete case analysis was performed.

All individuals managed with the CBP provided consent for their data to be included in this study. Participants were aged a mean (SD) 26 (10) years at injury, 39% were female and 49% had concomitant meniscal injury (38 stable vertical tears in posterior horn of medial and/or lateral meniscus and 1 displaced medial meniscus ramp lesion). Participant characteristics are reported in table 2 for all participants and by ACLOAS grade on 3-month MRI (grade 1 vs grades 23). Participant characteristics are presented separately for participants with an ACLOAS grades 2 and 3, in online supplemental appendix 3.

Participant characteristics

At 3-month follow-up, n=72 (90%) had a continuous ACL (n=40 (50%) ACLOAS grade 1, n=32 (40%) ACLOAS grade 2). Of the 8 patients with ACLOAS grade 3 on 3-month MRI, 6 ACLs had attached to the lateral wall (n=3) or lateral wall and posterior cruciate ligament (n=3). Between 3-month and 6-month MRI, 4 participants changed from ACLOAS grade 1 to grade 0 and 1 participant changed from ACLOAS grade 2 to grade 3 due to subsequent knee injury. ACLOAS grades from 3-month and 6-month MRIs (complete case analysis) are presented in online supplemental appendix 4. Other participants sustained the same ACLOAS grade at 3 months and 6 months. MRI examples of ACL healing for five participants are presented in figure 2.

MRI images demonstrating MRI evidence of ACL healing for five participants. ACL, anterior cruciate ligament; ACLOAS, Anterior Cruciate Ligament OsteoArthritis Score.

Participants with an ACLOAS grade 1 on 3 month MRI reported better patient-reported outcomes on the Lysholm Scale and ACLQOL (including all ACLQOL subscales) compared with participants with an ACLOAS grades 23 (table 3). Online supplemental appendix 2 presents outcomes separately for participants with an ACLOAS grades 2 and 3. Online supplemental appendix 5 depicts participant scores based on time post-injury and 3-month healing status. Participants with an ACLOAS grade 1 had reduced knee laxity and a higher proportion returned to pre-injury sport (92% vs 62%) compared with participants with an ACLOAS grades 23 (table 3).

Participant outcomes

Eleven (14%) participants re-injured their ACL (mean (SD): 10 months (4 months), range: 518 months), 4 had ACLOAS grade 1, and 7 had ACLOAS grade 2 on 3-month MRI. After re-injury, 9 of 11 participants underwent ACLR (mean: 2 months after re-injury, range: 06 months), 1 participant decided to undergo the CBP again (resulting in evidence of ACL healing on MRI, ACLOAS grade 1). Mechanisms of re-injury included AFL/rugby (n=3), basketball (n=1), skiing (n=1), cycling accident (n=1), netball (n=1), Oz-tag (n=1), wrestling (n=1), dancing (n=1) and climbing (n=1). The four participants who re-injured their ACL despite ACLOAS grade 1 on 3-month MRI, did so during high-speed skiing/cycling accidents (5 months and 18 months post-injury), rugby (contact injury 10 months post-injury) and AFL (contact injury 17 months post-injury).

Two of 80 (2.5%) participants underwent an arthroscopic knee surgery, one participant for cyclops lesion removal 7 months post-injury and another underwent a partial lateral meniscectomy 5 months post-injury. Thirty eight of 39 (97%) meniscal tears were asymptomatic following the CBP, including one displaced medial meniscus ramp lesion.

Two patients were diagnosed with a below knee DVT (before DVT prophylaxis was added to the protocol), which were identified in the second week of the CBP, and were successfully managed with therapeutic dosing of Clexane. Both patients completed the CBP. Follow-up Doppler ultrasound demonstrated complete resolution of the DVT for both patients. Thereafter (11th patient onwards), DVT risk mitigation strategies were deployed as described in the Methods section.

Most patients reported mild and transient discomfort while adapting to the brace during the first week, often citing an awkward or uncomfortable sleeping position with the knee fixed at 90. This discomfort resolved for all patients without intervention. No patients opted to exit the programme due to discomfort or complication. At the time of unrestricted knee flexion in the brace, a flexion contracture (typically 515) was observed in 11 patients (14%). This resolved in all patients with physiotherapy exercises within 3 weeks. Contralateral lower limb overuse injuries, including pes anserine bursitis (n=1), insertional hamstrings tendinopathy (n=1) and patellofemoral pain (n=3), were observed at the time of brace removal.

This case series found that 72 out of 80 (90%) people with acute ACL rupture who were managed with a novel bracing protocol involving immobilisation of the knee at 90 flexion, had evidence of ACL healing (a continuous ACL) on 3-month MRI. An ACLOAS grade 1 on 3-month MRI was associated with better 12-month knee function and QOL, reduced passive knee laxity and a higher rate of return-to-sport, compared with an ACLOAS grades 23.

A recent analysis of the KANON trial found that 16 of 54 (30%) participants randomised to initial rehabilitation and optional delayed ACLR had signs of ACL healing on a 2-year MRI.9 Of the 30 participants who were managed with rehabilitation alone, 53% had MRI evidence of ACL healing at 2 years.9 In comparison, applying the same criteria we observed ACL healing in 72 of 80 (90%) participants on 3-month MRI. Six of 8 ACLs with discontinuous fibres had attached to the lateral wallposterior cruciate ligament. Although we graded these as discontinuous, it is possible that attachment to these structures could provide some function/stability, and it is not clear how this compares to the function/stability of an ACL graft. The high rate of healing observed on 3-month MRI suggests that the CBP could be conducive to ACL healing. To explore this potential, further research, including mechanistic studies, is required. Interestingly, patients had a range of concomitant injuries at baseline which became asymptomatic after the CBP. Only 1 of 39 patients with concomitant meniscal injuries had persistent symptoms after the CBP and underwent meniscal surgery. It is possible that the CBP could be beneficial for healing of concomitant injuries, this warrants further research.

Additionally, 37 of 40 participants (93%) with an ACLOAS grades 23 on 3-month MRI had an ACL rupture with a partial femoral avulsion, compared with only 7 (18%) participants with an ACLOAS grade 1. Although outside the scope of this study, it is possible that characteristics of ACL rupture observed on acute MRI (including partial/complete femoral avulsion, the displacement of ACL tissues outside of the intercondylar notch and gap distance between the ruptured ACL stumps) are associated with the likelihood of ACL healing. Further studies are needed to explore this possibility, with potential to inform ACL injury management decisions.

The favourable outcomes observed in patients with signs of ACL healing in our study are supported by findings from the KANON trial. In the KANON trial, participants with an ACLOAS of 02 on a 2-year MRI reported better knee function and QOL compared with participants with ACL discontinuity, and people who had delayed or early ACLR.9 Notably, only 8 (10%) patients in our study had ACL discontinuity on a 3-month MRI, and we used a different cut-off when comparing outcomes between groups. Collectively, results from the KANON trial and CBP suggest there may be a spectrum of ACL healing, whereby a more normal MRI appearance of the ACL may be associated with favourable patient outcomes.

Surprisingly, patients with an ACLOAS grades 23 reported excellent Lysholm Scale scores on average, even though scores were lower than patients with an ACLOAS grade 1. A Lysholm median score of 98 reported by people with an ACLOAS grade 1 is better than mean scores reported 2471 months after ACLR using autograft (mean scores range from 85 to 95).16 In contrast, the difference in ACLQOL scores was large between people with lower and higher grades of ACL healing. People with an ACLOAS grade 1 reported a median (IQR) ACLQOL score of 89 (7696). In comparison, people managed with ACLR or rehabilitation alone, report mean ACLQOL scores in the range of 5076, across a variety of time-points after ACL injury.17 The ACLQOL scores reported by people with an ACLOAS grades 23 may be more comparable with ACLQOL scores reported after ACLR and management with rehabilitation alone.17 Examining the ACLQOL domain scores suggests the greatest differences were within the recreational and sport participation, lifestyle and social emotional domains, with smaller differences observed in the symptoms and physical complaints and work-related concern domains.

The lower proportion who returned to sport with an ACLOAS grades 23 (64%) compared with an ACLOAS grade 1 (92%) could partly explain the lower QOL in this group considering return-to-sport is a key determinant of QOL after ACL injury.18 These return-to-sport rates are high compared with studies in ACL reconstructed individuals, where a pooled average of 55% of non-professional athletes returned to sport after ACLR.10 It should also be noted that patients in our study were aware of the degree of healing observed on MRI. It is possible that patients who received feedback that they had a suboptimal healing result on MRI had lower knee confidence and negative mental impacts compared with patients who received more positive feedback. This could also contribute to lower QOL scores in these domains.

It is not known whether a continuous ACL observed on MRI reflects restoration of pre-injury ACL function. Although, the high self-reported knee function and return-to-sport rate in people with an ACLOAS grade 1 suggests a positive association with knee function. It is important to note that 11 patients (14%) had re-ruptured their ACL at the time of follow-up. The 4 patients who re-injured their ACL despite an ACLOAS grade 1 on a 3-month MRI did so during competitive sport (rugby/AFL contact injuries) or high-speed skiing/cycling accidents. It is not clear whether re-injury of the ACL is a reflection of reduced tensile strength of the ACL fibres, considering the mechanisms of re-injury were similar to the mechanisms of initial ACL rupture. The rate of re-injury observed in our study may be comparable with re-injury rates following ACLR, whereby approximately 1-in-5 young athletes suffer a rupture of the ACL graft or contralateral ACL, and around 90% of these injuries occur after return to high-risk sports.19 Interestingly, one patient elected to undergo the CBP after re-rupturing their ACL and achieved an ACLOAS grade 1 on a 3-month MRI and returned to sport (rugby), after re-completion of the CBP. Longer-term follow-up is required to gain greater understanding of survivorship of the healed ACL and the risk of subsequent knee injury following management with the CBP.

In view of the promising outcomes of this case series and the potential advantages of preserving the native ACL following injury, further research in this area is warranted. Prognostic studies are needed to determine whether certain presentations are less likely to heal when managed with the CBP. In the future, the potential for the ACL to heal may be an important consideration when deciding on surgical or non-surgical management. We found that signs of ACL healing were apparent on MRI as early as 3 months after ACL rupture. Three months is the typical duration that people trial initial rehabilitation before considering delayed ACLR. It is possible that 3-month MRI findings could identify patients who would benefit from ACLR. Only 10% of patients with an ACLOAS grade 1 at 3 months had progressed to an ACLOAS grade 0 at 6 months. Further research is needed to understand the timeline and stages of ACL healing. Additionally, clinical trials are needed to compare outcomes for patients managed with the CBP, compared with those who are managed with ACLR or rehabilitation alone. Of particular importance will be the investigation of re-injury rates, return-to-sport, patient-reported outcomes, functional stability and the prevalence of knee osteoarthritis.

Bridge enhanced ACL repair (BEAR) is a surgical technique that augments repair of the ligament with a scaffold implant (a resorbable protein-based implant containing autologous blood) positioned between the torn ends of a midsubstance ACL tear in attempt to facilitate healing.20 An interesting area for future research is the comparison of ACL healing on MRI and clinical outcomes following management with BEAR compared with the CBP. Additionally, there may be specific ACL rupture presentations that benefit from early surgical intervention to assist with facilitating ACL healing. For example, acute ACL injuries with a large gap distance between torn remnants and acute ACL injuries with displaced ACL tissue outside the intercondylar notch might benefit from surgery to reduce and realign the ACL tissues. There could also be a role for bracing in knee flexion postoperatively to protect the repair and/or reduction of the injured ACL tissues (akin to management of displaced bone fractures with open reduction internal fixation followed by a period of postoperative immobilisation). Further research is needed to explore this potential.

This was a pragmatic study, whereby data were collected in the course of clinical practice rather than in a research setting. For this reason, some adaptations were made to the CBP overtime. Our study design did not allow comparison of outcomes with people managed with ACLR or rehabilitation alone. There is also potential for selection bias. After the 50th patient was braced, patients were discouraged from undertaking the CBP if they had a femoral avulsion and/or ACL tissue displaced outside the boundaries of the intercondylar notch. Although 14 of 29 patients underwent the CBP despite this advice, 15 of these individuals chose ACLR. The overall proportion with an ACLOAS grade 1 at 3 months may have been lower if these 15 individuals had not received this advice and underwent the CBP. Tests of passive knee laxity were performed by two unblinded physicians and may be subject to detection and observer bias, a clinical trial, including blinding of examiners, is needed. Further studies may also benefit from using a knee arthrometer to collect more objective measures of knee laxity. MRIs were graded by three radiologists who were aware that patients had undertaken the CBP. Although this case series highlights the potential for positive outcomes using the CBP, larger cohorts with longer-term follow-up and, in particular, randomised clinical trials are needed.

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Healing of acute anterior cruciate ligament rupture on MRI and ... - British Journal of Sports Medicine

Princeton hangs on to hand 1st loss of season to Duquesne – TribLIVE

By now, its no secret Duquesnes basketball schedule was assembled with postseason aspirations in mind.

Not the College Basketball Invitational, where the Dukes made an appearance last season, mind you. Not even the National Invitation Tournament.

Were building this to get to the (Atlantic 10 Tournament) championship and to get to the (NCAA) Tournament, sophomore point guard Kareem Rozier said.

Its a hard schedule, coach Keith Dambrot said, reflecting on Duquesnes 70-67 loss to Princeton on Wednesday night. We felt like we were going to have a relatively good team, so why not?

Its results such as the Dukes first loss of the season that Rozier and his teammates are hoping, come March, will shape the Dukes into a Tournament-type team for the first time in nearly five decades.

I truly believe this is the team that will do it this year, Rozier said. But to do it, youve got to go through some rough patches, and this is one of them.

Duquesne and Princeton waited until the last second to settle their outcome before the Tigers edged the Dukes and sent a boisterous UPMC Cooper Fieldhouse crowd home disappointed.

Matt Allocco scored 23 points on 10-of-13 shooting and Princeton (3-0) withstood Duquesnes last-second rush to remain undefeated.

Duquesne trailed 68-67 with a chance to come away with a win in the closing seconds, but Fousseyni Drames contested layup clanged off the rim and Rozier fouled Princetons Xaiavian Lee with four-tenths of a second remaining.

Lee converted both free throws to seal the victory for Princeton.

Lee added 20 points and Blake Peters contributed 11 for The Tigers, who led Duquesne for nearly the entire game, trailing for just 46 seconds in the first half.

A classic giant slayer the Tigers last season reached the Sweet 16 as a No. 15 seed Princeton shot 56.5%.

The Tigers carried an impressive NCAA Evaluation Tool ranking of 93 following victories over Rutgers (NET ranking of 40) and Hofstra (85).

We had our shot tonight and it didnt fall in our favor, Rozier said. It wasnt our time, and thats OK. It hurts right now. Princeton would have been a great win.

Duquesne, with a NET ranking of 137, opened the season with impressive victories over Cleveland State (185) and College of Charleston (52). And theres more to come before the A-10 opener Jan. 3 at Massachusetts.

The Dukes will face Nebraska (92) next week and four other opponents later on with impressive NET rankings: Bradley (78), Marshall (83), Santa Clara (87) and UC Irvine (102).

On Tuesday, UC Irvine and Santa Clara knocked off Power 5 conference teams, the Anteaters upsetting No. 16 Southern California and the Broncos defeating Stanford.

We have enough guys, Dambrot said.

But two big men that Dambrot has been counting on Dusan Mahorcic and Tre Williams are sidelined indefinitely by injuries.

Mahorcic, a 6-foot-10, 235-pound transfer from North Carolina State, has yet to play while working his way back from a serious knee injury. During a pregame interview on SportsNet Pittsburgh and ESPN Plus, Mahorcic said he was expecting to receive two additional Platelet-rich plasma injections and hoped to make his Duquesne debut in a month to six weeks.

The 6-7, 250-pound Williams, who sustained a hand injury on Friday against Charleston, is due back sooner than later, unless he has a complication, Dambrot said.

Until then, Duquesne will survive, he said.

But the Dukes ran into trouble Wednesday, though Dambrot quipped, If we make (the last shot), were all happy.

Jimmy Clark III led Duquesne (3-1) with 17 points. Dae Dae Grant added 16 for the Dukes, who return to UPMC Cooper Fieldhouse on Friday against Rider in a continuation of the Cornhusker Classic. The Dukes defeated Stony Brook on Monday in the first round.

Duquesne trailed at halftime for the third time in its first four games, but it couldve been by a wider margin had former Our Lady of Sacred Heart star Jake DiMichele, inserted late in the first half, not hit a 3-point shot at the buzzer for his first college points to cut the Princeton lead to 37-31.

A Grant 3-pointer pulled Duquesne within 52-49, and he nearly tied the score on the next possession, but his long attempt from the behind the arc bounded off the back of the iron and out of bounds.

Princeton then scored six unanswered points to go up 58-49.

Clark, who went to the bench briefly with his fourth foul at the 11:02 mark, returned and promptly swished a 3-pointer to cut the Princeton lead to 58-54.

A pair of Rozier free throws with 4:34 left kept Duquesne close at 63-60 and the Dukes defense then trapped Princeton into calling a timeout before the Tigers could escape.

Princeton lost possession and Drame scored on a driving layup to pull Duquesne within 63-62, igniting a crowd infused with an unusually rowdy Dukes student section.

Zach Martinis three-point play gave Princeton some breathing room again at 66-62 before Duquesne responded when Clark scored on a driving layup and was fouled. He converted the free throw to again pull Duquesne within a point, 66-65, with 1:45 left.

Alloccos acrobatic shot underneath for Princeton kept the the Tigers in control, but Grant hit a pair of free throws at the other end to make it 68-67.

The hectic early season schedule includes seven games in November for Duquesne, which appeared a step slow, at times, against Princetons methodic approach.

Its a tough team to play at the beginning of the year, Dambrot said. It was a tough game. Our guys battled to the end. Our guys are gutty guys. They played hard. They didnt quite have it, but they hung around and hung around and gave ourselves a good chance to win.

Looking relaxed, despite his teams first loss, Dambrot stood up, forced a weak smile and said, See ya next See ya in 24 hours.

Dave Mackall is a Tribune-Review contributing writer.

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Princeton hangs on to hand 1st loss of season to Duquesne - TribLIVE

UK first to approve CRISPR treatment for diseases: what you need to … – Nature.com

Sickle-cell anaemia is marked by red blood cells that are misshapen and sticky, affecting blood flow.Credit: Eye Of Science/SPL

In a world first, the UK medicines regulator has approved a therapy that uses CRISPR gene editing as a treatment for diseases. The decision marks another high point for a biotechnology that has regularly been lauded as revolutionary in the decade since its discovery.

The therapy, called Casgevy, will treat the the blood conditions sickle-cell disease and -thalassaemia. Sickle-cell disease, also known as sickle-cell anaemia, can cause debilitating pain, and people with -thalassaemia can require regular blood transfusions.

This is a landmark approval which opens the door for further applications of CRISPR therapies in the future for the potential cure of many genetic diseases, said Kay Davies, a geneticist at the University of Oxford, UK, in comments to the UK Science Media Centre.

Nature explains the research behind the treatment and explores whats next.

The approval by the Medicines and Healthcare products Regulatory Agency (MHRA) follows promising results from clinical trials that tested the one-time treatment, which is administered by intravenous infusion and was developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland.

The trial for sickle-cell disease has followed 29 out of 45 participants long enough to draw interim results. Casgevy completely relieved 28 of those people of debilitating episodes of pain for at least one year after treatment.

Researchers also tested the treatment for a severe form of -thalassaemia, which is conventionally treated with blood transfusions roughly once a month. In this trial, 54 participants received Casgevy and 42 patients have participated for long enough to provide interim results. For at least one year after treatment, 39 participants, or 93% of those treated, did not need a red-blood-cell transfusion. The remaining three people had their need for blood transfusions reduced by more than a 70%.

Casgevy relies on the gene-editing tool CRISPR, the developers of which won the Nobel Prize in Chemistry in 2020.

Sickle-cell disease and -thalassaemia are caused by errors in the DNA sequence of genes that encode for haemoglobin, a molecule that helps red blood cells to carry oxygen around the body.

In sickle-cell disease, abnormal haemoglobin makes blood cells misshapen and sticky, causing them to form clumps that can clog blood vessels. These blockages reduce the oxygen supply to tissues, which can cause periods of severe pain, known as pain crises.

-thalassaemia occurs when mutations in the haemoglobin gene lead to deficient or absent levels of the oxygen-carrying molecule in red blood cells, low numbers of red blood cells and symptoms such as fatigue, shortness of breath and irregular heartbeats.

Clinicians administer Casgevy by taking blood-producing stem cells out of the bone marrow of people with either disease and using CRISPR to edit genes encoding for haemoglobin in these cells. The gene-editing tool an RNA molecule that guides the enzyme to the correct region of DNA and a Cas9 enzyme that cuts DNA.

Once the Cas9 enzyme reaches the gene targeted by Casgevy, called BCL11A, it cuts both DNA strands. BCL11A usually prevents the production of a form of haemoglobin that is made only in fetuses. By disrupting the BCL11A gene, Casgevy unleashes the production of fetal haemoglobin, which does not carry the same abnormalities as adult haemoglobin in people with sickle cell or -thalassaemia patients.

Before the gene-edited cells are infused back into the body, people must undergo a treatment that prepares the bone marrow to receive the edited cells. Once administered, the stem cells give rise to red blood cells containing fetal haemoglobin. After some time, this relieves symptoms by boosting the oxygen supply to tissues. Patients may need to spend at least a month in a hospital facility while the treated cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin, the MHRA said in a press release.

Participants involved in the trials, which are ongoing, experienced side effects including nausea, fatigue, fever and an increased risk of infection, but no significant safety concerns were identified. The MHRA and manufacturer are monitoring the safety of the technology and will release further results.

One concern surrounding the approach is that CRISPR can sometimes make unintended genetic modifications with unknown side effects.

It is well known that CRISPR can result in spurious genetic modifications with unknown consequences to the treated cells, geneticist David Rueda at Imperial College London told the SMC. It would be essential to see the whole-genome sequencing data for these cells before coming to a conclusion. Nonetheless, this announcement makes me feel cautiously optimistic."

The US Food and Drug Administration is considering approval of Casgevy, whose generic name is exa-cel, for sickle-cell disease; its advisers met last month to discuss the therapy. The European Medicines Agency is also reviewing the treatment for both diseases.

For now, the therapy is likely to remain the reserve of rich nations with developed health-care systems. This treatment may not easily scale up to be able to provide treatments in low- and middle-income countries, since it requires the technology to obtain a patients blood stem cells, deliver the genetic editor to these stem cells, and then reinjection of these cells, geneticist Simon Waddington at University College London told the SMC. It is not an off the shelf medicine that can be readily injected or taken in pill form, he says.

Even in places where it win approval, the high cost of Casgevy is likely to limit who can benefit from it.

The challenge is that these therapies will be very expensive so a way of making these more accessible globally is key, said Davies.

The treatments price has not yet been settled in the United Kingdom, but estimates suggest that it could cost roughly US$2 million per patient, in line with the pricing of other gene therapies.

We have not established a list price for the UK at this time and are focused on working with the health authorities to secure reimbursement and access for eligible patients as quickly as possible, a Vertex spokesperson told Nature.

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UK first to approve CRISPR treatment for diseases: what you need to ... - Nature.com

Sickle-Cell Treatment Created With Gene Editing Wins U.K. Approval – The New York Times

Regulators in Britain on Thursday approved the first treatment derived from CRISPR, the revolutionary gene-editing method. Called Casgevy, the treatment is intended to cure sickle-cell disease and a related condition, beta thalassemia.

The manufacturers, Vertex Pharmaceuticals, based in Boston, and CRISPR Therapeutics, based in Switzerland, say about 2,000 patients in Britain with sickle-cell disease or beta thalassemia are expected to be eligible for its treatment.

The companies anticipate that the Food and Drug Administration will approve Casgevy for sickle-cell patients in the United States in early December. The agency will decide on approval for beta thalassemia next year.

In late December, the F.D.A. is expected to approve another sickle cell gene therapy by Bluebird Bio of Somerville, Mass. That treatment does not rely on gene editing, insteading using a method that inserts new DNA into the genome.

Sickle-cell disease is caused by a defective gene that leads to the creation of abnormal hemoglobin, the oxygen-carrying component in red blood cells. The cells themselves become malformed, causing episodes of extreme pain. About 100,000 Americans, who are mostly Black and Hispanic, are believed to have the illness.

In beta thalassemia, the defective gene leads to deficient levels of hemoglobin in red blood cells. The condition is rare.

Casgevy relies on CRISPR to nick the DNA, activating a gene that produces an alternative form of hemoglobin. To receive the sickle-cell treatment, patients in Britain must be at least 12 years old and have experienced repeated episodes of extreme pain.

There is no upper age limit, nor are patients excluded because they have suffered too much organ damage from sickle-cell disease, said Dr. David Altshuler, Vertexs chief scientific officer.

But the patients must have no other options. Sickle-cell disease can be cured with a bone-marrow transplant, but few patients have compatible donors.

For people struggling with the illness, the Vertex and Bluebird treatments have been a long time coming. Pain is not the only complication people with sickle-cell disease also suffer bone and organ damage and strokes. The misshapen blood cells do not survive long, resulting in anemia.

Still, the CRISPR and Bluebird treatments are onerous and will require expertise that most hospitals lack.

Patients must receive intense chemotherapy to clear their bone marrow of abnormal stem cells and make room for the genetically altered cells. Then the patients must stay a month or more in a hospital while their marrow regrows.

And gene editing is expensive. Vertex and CRISPR Therapeutics have not set a price yet in Britain that will depend on conversations with those who will be paying for it, said Stuart Arbuckle, executive vice president and chief operating officer at Vertex.

The price in the United States, though, is expected to be millions of dollars per patient. Sickle-cell disease itself is expensive, however, costing the U.S. health system an estimated $3 billion a year.

In the United States, Bluebird already has a gene therapy approved for beta thalassemia. It costs $2.8 million per patient.

Dr. Altshuler said Vertex was testing its sickle-cell treatment in children ages 5 to 11, hoping to prevent the irreversible organ damage that occurs over time.

The companys first sickle-cell patient, Victoria Gray, said on Thursday that the treatment changed her life.

Ms. Gray, a Walmart associate in Forest, Miss., was diagnosed with sickle-cell disease when she was 3 months old and had a pain crisis. Those episodes became a part of her life, resulting in frequent hospitalizations.

A lot of my dreams, I couldnt do, she said. The smallest things cold, changing weather I would end up in the hospital.

She had the gene editing treatment in 2019, when she was 33. Now, she said, all her symptoms have vanished.

It meant a new beginning, Ms. Gray said. It is more than I ever dreamed of, for everything to be gone.

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Sickle-Cell Treatment Created With Gene Editing Wins U.K. Approval - The New York Times