Xin Chen
University of Texas Southwestern Medical Center, TX·Genetics
Some inherited diseases come from a single broken gene, and many of them damage the nervous system in childhood with no cure available. One strategy is gene replacement: package a healthy copy of the gene inside a harmless virus shell, deliver it to nerve cells, and let those cells make the missing protein again.
- Fields
Genetics
Neuroscience
Medicine & Clinical Research
- Topics
gene therapy
gene replacement therapy
adeno-associated virus
- Grants
- 2 known grants, through Apr 2028
What they work on
- Test whether AAV9fyhr-delivered PDHA1, injected into the spinal fluid of E75A mice at several doses and at young or older ages, improves behavior and corrects metabolic measures in this model of pyruvate dehydrogenase complex deficiency.
- Determine the safety of escalating intrathecal doses of AAV9fyhr/PDHA1 in wild-type C57BL/6J mice, using in-life monitoring and full histopathology focused on dorsal root ganglia toxicity and liver injury.
- Evaluate AAV9/GDAP1 gene replacement in Gdap1 knockout rats modeling CMT4A, dosing before and after symptom onset and measuring transgene expression, behavior, nerve conduction velocity and peripheral nerve pathology.
- Ask whether AAV9-delivered GDAP1 can produce enough functional protein to outcompete the dominant-negative allele in heterozygous Gdap1 R120W knock-in rats, the model of late-onset CMT2K.
- Assess dose-responsive toxicity of AAV9/GDAP1 in treated rats through comprehensive in-life monitoring and postmortem assessment, to build supporting safety evidence for an investigational new drug application.
More about the research
Work here applies that strategy to two different genetic diseases, using adeno-associated virus type 9 (AAV9), a virus vector that reaches the brain, spinal cord and nerves. Both projects follow the same logic: inject the vector into the fluid around the spinal cord in animal models of the disease, then ask whether symptoms improve and whether the treatment is safe at higher doses. The grants state that the lab has over 20 years of experience developing gene therapies for neurological conditions and that eight candidates from the lab have advanced to clinical trials.
Why it matters
Children with PDHA1 deficiency currently have no curative option and most die before age four, and CMT neuropathies affect roughly one in 2,500 people with progressive weakness and sensory loss. If these animal studies show benefit without toxicity, they could supply the efficacy and safety evidence needed to move gene replacement toward first-in-human trials for these diseases, and could also establish AAV9fyhr as a general way to deliver genes to the central nervous system for other neurological disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Arun Srivastava
University of Florida, FL·Medicine & Clinical Research
Develop liver-de-targeted, capsid- and genome-modified next-generation AAV vectors based on AAVrh74 for skeletal muscle and AAV9 for the central nervous system, and demonstrate enhanced expression from AAV-PDHA1 vectors.
Steven Gray
University of Texas Southwestern Medical Center, TX·Medicine & Clinical Research
Assess the safety and toxicology of AAV9/AGA, a harmless adeno-associated virus carrying a working copy of the AGA gene, in preclinical models following intrathecal injection into the fluid around the spinal cord.
Stephen Kaler
Columbia University, NY·Medicine & Clinical Research
Evaluate the preclinical safety and tolerability of AAV9 gene therapy delivering a shortened, codon-optimized ATP7A copper transporter gene for Menkes disease.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
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