Spur Therapeutics Presents Promising New Data from its GBA1 Parkinson’s Disease Research Program
2024年7月1日 - 8:00PM
Spur Therapeutics, formerly Freeline Therapeutics, today announced
new data from its GBA1 Parkinson’s disease research program
demonstrating that its rationally engineered GCase85 enzyme reduces
the accumulation of α-Synuclein, a protein that plays a significant
role in the development and progression of Parkinson’s disease,
more effectively than wildtype glucocerebrosidase (GCase) in in
vitro studies. These data were presented at the inaugural GBA1
meeting, hosted by the Montreal Neurological Institute-Hospital at
McGill University and sponsored by The Michael J. Fox Foundation,
Parkinson Canada, The Silverstein Foundation, the Hilary &
Galen Weston Foundation and Cure Parkinson’s with the aim of
advancing the understanding and treatment of GBA1-associated
neurodegenerative diseases.
“There is a rapidly growing body of evidence that GBA1 mutations
and the resulting deficiency of the GCase enzyme play a significant
role in driving neurodegenerative processes in Parkinson’s disease
as well as certain forms of dementia,” said Henning Stennicke, PhD,
Chief Scientific Officer of Spur Therapeutics. “We’re pleased to
share data from our GBA1 Parkinson’s research program,
demonstrating that our rationally engineered GCase85 enzyme results
in more robust exposure than wildtype GCase and broader
distribution in the brain in both in vitro and in vivo models of
disease, as well as greater reduction of the α-Synuclein
accumulation that is a hallmark of Parkinson’s disease. We believe
the enhanced stability of GCase85 provides the opportunity to
develop a potentially best-in-class gene therapy for Parkinson’s
disease patients with GBA1 mutations.”
Spur’s research program in Parkinson’s disease builds on its
work in Gaucher disease and is focused on a subset of Parkinson’s
disease patients with mutations in the GBA1 gene, the same gene
implicated in Gaucher disease. In both Gaucher and Parkinson’s,
GBA1 mutations lead to a deficiency of the GCase enzyme and the
accumulation of harmful substrates. GBA1 mutations greatly increase
the risk of developing Parkinson’s disease and are associated with
earlier onset of disease, more severe symptoms and increased
likelihood of progression to dementia.
Spur scientists originally designed the GBA1-85 transgene to
deliver GCase85, a rationally engineered version of GCase with
enhanced stability over wildtype, as part of its work on FLT201,
the company’s clinical-stage gene therapy program in Type 1
Gaucher’s disease. Early data from the ongoing Phase 1/2 clinical
trial of FLT201 has shown significant reductions in accumulated
substrate and compelling signs of clinical benefit as well as a
favorable safety and tolerability profile. Leveraging the same
transgene, Spur now aims to develop a potentially life-changing
gene therapy candidate for Parkinson’s disease patients with GBA1
mutations.
The data presented at the GBA1 Meeting show:
- GCase85 results in an order of magnitude higher GCase activity
compared to wildtype in vitro and in vivo.
- GCase85 is more efficient at reducing α-Synuclein accumulation
compared to wildtype in neuronal cells in vitro.
- Direct injection into the caudate putamen region of the brain
using an AAV9 vector results in efficient distribution to the
target cells within the substantia nigra, which is a key area of
the brain affected by Parkinson’s disease.
- An AAV9-GBA1-85 construct results in stronger expression and
broader GCase distribution in the brain than a wildtype AAV9-GBA1
construct when directly injected into the brain in mice.
Spur is working to further optimize GCase85 for expression in
the brain and identify the best capsid and route of administration
for delivery of its proprietary GBA1-85 transgene to key areas of
the brain affected by Parkinson’s disease. The company expects to
select a development candidate in the second half of 2024 to
progress into preclinical studies designed to support the program’s
advancement into clinical trials.
About GBA1 Parkinson’s DiseaseParkinson’s
disease (PD) is a progressive neurodegenerative disorder that
results in tremors, muscle rigidity, difficulty walking, anxiety,
depression and cognitive impairments. Approximately 5-15% of PD
patients have mutations in the GBA1 gene, which encodes for the
glucocerebrosidase (GCase) enzyme. The most common genetic risk
factor for PD, GBA1 mutations significantly increase the risk of
developing PD and are associated with earlier onset and more severe
disease. There are no approved disease-modifying therapies for PD,
and current treatments, which focus on managing symptoms, become
less effective over time. Spur estimates GBA1 PD affects
approximately 190,000 patients in the United States, United
Kingdom, France, Germany, Spain and Italy.
About Spur TherapeuticsSpur Therapeutics is a
clinical-stage biotechnology company focused on developing
life-changing gene therapies for debilitating chronic conditions.
By optimizing every component of its product candidates, Spur aims
to unlock the true potential of gene therapy to realize outsized
clinical results. Spur is advancing a breakthrough gene therapy
candidate for Gaucher disease and a potential first-in-class gene
therapy candidate for adrenomyeloneuropathy, as well as a research
strategy to move gene therapy into more prevalent diseases,
including forms of Parkinson’s, dementia, and cardiovascular
disease. Expanding our impact, and advancing the practice of
genetic medicine.
Toward life-changing therapies, and brighter futures. Toward
More™
For more information, visit www.spurtherapeutics.com or connect
with Spur on LinkedIn and X.
ContactNaomi
Aokinaomi.aoki@spurtherapeutics.com+ 1 617 283 4298