Gain Therapeutics Presents Preclinical GT-02287 Data at Neuroscience 2024
Gain Therapeutics presented new preclinical data for GT-02287 at the Society for Neuroscience 2024 conference. The data demonstrates disease-modifying activity in both GBA-1 and idiopathic Parkinson's disease models. Key findings include:
1. Persistent rescue of motor and cognitive function after GT-02287 discontinuation
2. Improved mitochondrial function and neuroprotection in GBA1-Parkinson's disease models
3. Reduction in Tau accumulation in GBA-1 mutation and wild type cell lines
The results suggest GT-02287's potential as a disease-modifying therapy for Parkinson's disease and possibly Alzheimer's disease and other tauopathies. The compound showed positive effects on mitochondrial and lysosomal health, addressing the disease cascade resulting from GCase dysfunction.
Gain Therapeutics ha presentato nuovi dati preclinici per GT-02287 alla conferenza della Society for Neuroscience 2024. I dati dimostrano attività modificante la malattia sia nei modelli di malattia di Parkinson GBA-1 che idiopatica. I principali risultati includono:
1. Recupero persistente delle funzioni motorie e cognitive dopo la sospensione di GT-02287
2. Funzione mitocondriale e neuroprotezione migliorate nei modelli di malattia di Parkinson GBA1
3. Riduzione dell'accumulo di Tau nelle linee cellulari con mutazione GBA-1 e tipo selvatico
I risultati suggeriscono il potenziale di GT-02287 come terapia modificante la malattia per la malattia di Parkinson e possibilmente per la malattia di Alzheimer e altre tauopatie. Il composto ha mostrato effetti positivi sulla salute mitocondriale e lisosomiale, affrontando la cascata patologica risultante dalla disfunzione di GCase.
Gain Therapeutics presentó nuevos datos preclínicos para GT-02287 en la conferencia de la Society for Neuroscience 2024. Los datos demuestran actividad modificadora de la enfermedad en modelos de enfermedad de Parkinson GBA-1 e idiopática. Los hallazgos clave incluyen:
1. Rescate persistente de la función motora y cognitiva tras la discontinuación de GT-02287
2. Mejora de la función mitocondrial y neuroprotección en modelos de enfermedad de Parkinson GBA1
3. Reducción en la acumulación de Tau en líneas celulares con mutación GBA-1 y tipo salvaje
Los resultados sugieren el potencial de GT-02287 como una terapia modificadora de la enfermedad para la enfermedad de Parkinson y posiblemente para la enfermedad de Alzheimer y otras tauopatías. El compuesto mostró efectos positivos en la salud mitocondrial y lisosomal, abordando la cascada de la enfermedad resultante de la disfunción de GCase.
Gain Therapeutics는 Society for Neuroscience 2024 회의에서 GT-02287에 대한 새로운 전임상 데이터를 발표했습니다. 이 데이터는 질병 수정 활동을 GBA-1 및 특발성 파킨슨병 모델 모두에서 보여줍니다. 주요 발견 사항은 다음과 같습니다:
1. GT-02287 중단 후 운동 및 인지 기능의 지속적인 회복
2. GBA1-파킨슨병 모델에서 미토콘드리아 기능 및 신경 보호 개선
3. GBA-1 돌연변이 및 야생형 세포주에서 타우 축적 감소
이 결과는 GT-02287가 파킨슨병과 아마도 알츠하이머병 및 기타 타우병의 질병 수정 치료제로서의 잠재력을 시사합니다. 이 화합물은 GCase 기능 부전으로 인한 질병의 연쇄 반응을 해결하며 미토콘드리아와 리소좀 건강에 긍정적인 영향을 미쳤습니다.
Gain Therapeutics a présenté de nouvelles données précliniques pour GT-02287 lors de la conférence de la Society for Neuroscience 2024. Les données démontrent une activité modifiant la maladie à la fois dans les modèles de maladie de Parkinson GBA-1 et idiopathique. Les résultats clés incluent :
1. Sauvetage persistant de la fonction motrice et cognitive après l'arrêt de GT-02287
2. Amélioration de la fonction mitochondriale et de la neuroprotection dans les modèles de maladie de Parkinson GBA1
3. Réduction de l'accumulation de Tau dans les lignées cellulaires avec mutation GBA-1 et de type sauvage
Les résultats suggèrent le potentiel de GT-02287 en tant que thérapie modifiant la maladie pour la maladie de Parkinson et éventuellement la maladie d'Alzheimer ainsi que d'autres tauopathies. Le composé a montré des effets positifs sur la santé mitochondriale et lysosomale, s'attaquant à la cascade pathologique résultant de la dysfonction de GCase.
Gain Therapeutics stellte neue präklinische Daten zu GT-02287 auf der Konferenz der Society for Neuroscience 2024 vor. Die Daten zeigen krankheitsmodifizierende Aktivität sowohl in Modellen der GBA-1- als auch der idiopathischen Parkinson-Krankheit. Wichtige Erkenntnisse umfassen:
1. Persistente Rettung der motorischen und kognitiven Funktionen nach Absetzen von GT-02287
2. Verbesserte mitochondriale Funktion und Neuroprotektion in GBA1-Parkinson-Krankheitsmodellen
3. Reduzierung der Tau-Akkumulation in GBA-1-Mutations- und Wildtyp-Zelllinien
Die Ergebnisse deuten auf das Potenzial von GT-02287 als krankheitsmodifizierende Therapie für die Parkinson-Krankheit und möglicherweise auch für die Alzheimer-Krankheit und andere Tauopathien hin. Der Wirkstoff zeigte positive Effekte auf die mitochondriale und lysosomale Gesundheit und adressierte die Krankheitskaskade, die aus der GCase-Dysfunktion resultiert.
- GT-02287 demonstrated disease-modifying activity in both GBA-1 and idiopathic Parkinson's disease models
- Persistent rescue of motor and cognitive function after GT-02287 discontinuation
- Improved mitochondrial function and neuroprotection in GBA1-Parkinson's disease models
- Reduction in Tau accumulation in GBA-1 mutation and wild type cell lines
- Potential application for Alzheimer's disease and other tauopathies
- None.
GT-02287 Demonstrates Disease Modifying Capacity in Both GBA1 and Idiopathic Parkinson’s Disease Models
GT-02287 Improves Mitochondrial Function and Provides Neuroprotective Effect in GBA1-Parkinson’s Disease Models
GT-02287 Prevents Tau Accumulation in a Cellular Model
BETHESDA, Md., Oct. 07, 2024 (GLOBE NEWSWIRE) -- Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a clinical-stage biotechnology company leading the discovery and development of the next generation of allosteric small molecule therapies, today announced the presentation of new evidence supporting the disease-modifying activity of GT-02287 in preclinical animal models of both GBA-1 and idiopathic Parkinson’s disease during a late-breaker poster session yesterday at the Society for Neuroscience (SfN) 2024 conference that is being held October 5-9 in Chicago, IL. In animal models of GBA-1 and idiopathic Parkinson’s disease, rescue of motor and cognitive function associated with administration of GT-02287 was observed to be persistent upon wash out of GT-02287 without significant effect in performance for more than a week following discontinuation when compared to the animals in which treatment was continued.
Another presentation for GT-02287 yesterday described its association with improved mitochondrial function and neuroprotection in GBA1-Parkinson’s disease models.
Finally, a second late-breaker was presented describing the reduction in Tau accumulation associated with GT-02287 in both GBA-1 mutation and wild type cell lines, suggesting GT-02287 may have broader potential as a treatment for tauopathies such as Alzheimer’s disease.
“The robust preclinical development dossier for GT-02287 presented further strengthen our belief that GT-02287 has the potential to be a disease-modifying therapy for people suffering from Parkinson’s disease. The data demonstrate rescue of motor deficit and prevention of development of deficits in cognition which persisted even once the compound was removed. Moreover, GT-02287 demonstrated a positive effect on mitochondrial health as well as on lysosomal health which further demonstrates that the molecule acts throughout the disease cascade resulting from dysfunction of the lysosomal enzyme glucocerebrosidase (GCase), which GT-02287 was designed to target. Additionally, GT-02287 prevented Tau accumulation in human cellular models which demonstrates its potential to be a treatment for Alzheimer’s disease and other tauopathies,” commented Joanne Taylor, Ph.D., Senior Vice President of Research at Gain
“The preservation of motor and cognitive improvement in animal models of Parkinson’s disease associated with GT-02287 after its discontinuation coupled with the neuroprotective effects after delayed administration support the potential of GT-02287 to slow or stop the progression of Parkinson’s disease,” said Gene Mack, Interim CEO and CFO of Gain Therapeutics. “The potential of GCase as a therapeutic target beyond Parkinson’s Disease is an encouraging finding that we can incorporate into our future development plans for GT-02287.”
The late-breaking poster titled, “GT-02287, a clinical stage GCase regulator, demonstrates disease modifying capacity in both GBA1 and idiopathic Parkinson’s disease models,” was presented on-site October 6 at 3pm CT. In animal models of both GBA1 and idiopathic Parkinson’s disease, GT-02287 was administered after a clinical phenotype was established and then withdrawn from half the animals for more than one week prior to conclusion of the study. Neuromuscular function, motor coordination, and activities of daily living/cognition were measured in wire hang, beam walk, and nest building tests, respectively, throughout the study. GT-02287 was shown to rescue deficits in neuromuscular function and motor coordination in both models as well as to prevent the development of deficits in cognition and activities of daily living. Notably, withdrawal of GT-02287 for more than one week did not significantly affect performance in any of the tests, suggesting a disease modifying effect.
The poster titled, “GT-02287, a clinical stage GCase regulator, improves mitochondrial function and provides a neuroprotective effect in GBA1-Parkinson's disease models,” was presented on-site October 6 at 10am CT. In an in vitro model - in which cultured rat mesencephalic dopaminergic neurons were treated with conduritol beta epoxide (CBE) to cause partial knockdown of GCase activity comparable to that seen in PD patients carrying heterozygous GBA1 mutations (GBA1 is the gene encoding GCase)- treatment with GT-02287 reduced the level of mitochondrial reactive oxygen species (ROS) as well as ameliorating lysosomal pathology, reducing α-synuclein aggregation, and providing a neuroprotective effect. In an in vivo model in which mice were subjected to toxic insult by CBE and injection of α-synuclein preformed fibrils (PFFs) into the striatum – delayed administration of GT-02287 reduced levels of mitochondrial protein Miro1, an important maker for mitophagy; aggregated α-synuclein and plasma neurofilament light chain (NfL), a marker of neurodegeneration; as well as completely restoring motor function to control levels.
The late-breaking poster titled, “GT-02287, a GCase modulator and Gain Therapeutics’ PD drug candidate prevents Tau accumulation in a cellular model,” was presented on-site October 6 at 1pm CT. Lysosomal Tau accumulation was quantified in human fibroblasts, carrying either the L444P mutant or wild-type (WT) GBA engineered to express labelled Tau protein, at basal conditions as well in the presence of Alzheimer’s brain-derived Tau seeds. Basal and seed-induced Tau accumulation was significantly higher in Tau-GBA L444P cells, which express defective GCase, compared to Tau WT GBA cells. Treatment with GT-02287 reduced Tau accumulation in both cells carrying the L444P GBA mutation and those carrying wild-type GBA, demonstrating GT-02287’s potential as a disease-modifying treatment for Alzheimer’s disease and other tauopathies. This work was carried out in collaboration with scientists in the group of Professor Paolo Paganetti at the Laboratories for Translational Research of the Ente Ospedaliero Cantonale (LRT-EOC) in Bellinzona, Switzerland. This study was conducted under the support of an Innosuisse-Swiss Innovation Agency grant with the LRT-EOC and the Università della Svizzera italiana-affiliated Institute for Research in Biomedicine in Bellinzona, Switzerland.
PDFs of the posters presented at Neuroscience 2024 are available on the Science and Technology section of the Company’s website at https://gaintherapeutics.com/science-and-technology/posters.
About GT-02287
Gain Therapeutics’ lead drug candidate, GT-02287, is in clinical development for the treatment of Parkinson’s disease with or without a GBA1 mutation. The orally administered, brain-penetrant small molecule is an allosteric protein modulator that restores the function of the lysosomal protein enzyme glucocerebrosidase (GCase) which becomes misfolded and impaired due to mutations in the GBA1 gene, the most common genetic abnormality associated with PD, or other age-related stress factors. In preclinical models of PD, GT-02287 restored GCase enzymatic function, reduced aggregated α-synuclein, neuroinflammation and neuronal death, increased dopamine levels and improved motor function and cognitive performance. Additionally, GT-02287 significantly reduced plasma neurofilament light chain (NfL) levels, an emerging biomarker for neurodegeneration.
Compelling preclinical data in mouse models of GBA1-PD, including that presented at FENS Forum 2024 in June describing improvement in cognitive performance in addition to motor performance after administration of GT-02287, suggests that GT-02287 may have the potential to slow the progression of Parkinson’s disease.
Gain’s lead program in Parkinson’s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse – Swiss Innovation Agency.
About Gain Therapeutics, Inc.
Gain Therapeutics, Inc. is a clinical-stage biotechnology company leading the discovery and development of next generation allosteric therapies. Gain’s lead drug candidate, GT-02287 is currently being evaluated for the treatment of Parkinson’s disease with or without a GBA1 mutation. Results from a Phase 1 study of GT-02287 in healthy volunteers demonstrated favorable safety and tolerability, plasma exposure in the projected therapeutic range, CNS exposure, and target engagement and modulation of GCase enzyme.
Gain’s unique approach enables the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function. Deploying its highly advanced Magellan™ platform, Gain is accelerating drug discovery and unlocking novel disease-modifying treatments for untreatable or difficult-to-treat disorders including neurodegenerative diseases, rare genetic disorders and oncology.
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