December 17, 2021

The Promise of Gene Therapy in Neurological Disorders (Podcast)

Advanced genomic research techniques show potential to treat a variety of conditions

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Earlier this year, more than 30 years after the Human Genome Project began, scientists sequenced the complete human genome. The field continues to evolve rapidly.

“What we learned even four years ago is old school compared to what we know today in the field of genetics,” says Dennis Lal, PhD, MS, assistant professor and assistant staff in Cleveland Clinic’s Genomic Medicine Institute and Neurological Institute. “You will be able to better care for your patients with all this new knowledge that is available.”

In the latest episode of Cleveland Clinic’s Neuro Pathways podcast, Dr. Lal discusses advances in genomic research that show promise for targeted gene therapy for neurological disorders. He examines:

  • What we know today about the genome
  • The complication of heterogeneity (i.e., that one gene does not necessarily equal one disorder)
  • The development of genetic risk scores for diseases ranging from Alzheimer’s to epilepsy
  • The state of gene therapy for common versus rare neurological disorders
  • Current research projects, including the new Cleveland Clinic Brain Study of neurodegenerative disorders

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Neuro Pathways episodes at clevelandclinic.org/neuropodcast or wherever you get your podcasts.

Advertisement

Excerpt from the episode

Podcast host Glen Stevens, DO, PhD: So, the goal is to identify the right genes and the right patients that would fit the therapy correctly. Where are we in that?

Dr. Lal: This is quite interesting. When it comes to moving toward genetic or targeted therapy, there’s typically a game plan. The first part is identifying the “causal gene.” However, in the end, geneticists do not “identify” a gene since a gene cannot cause disease; what causes the disease is a pathogenic mutation, which leads to an abnormal version of the gene and a wrongly built protein. And then, typically, what people do is they try to match patients by molecular type of defect (mutation and gene). What genetics told us is that a single disease, such as stroke or Alzheimer’s, can be explained by many different genes. So there is more molecular heterogeneity, which also correlates with clinical heterogeneity.

Once it’s figured out which gene produces which subtype of the disease, then people also have clinical biomarkers like endpoints that can be used in a clinical trial. And then people try to develop therapies where you, for example, replace the gene using a virus, which brings a healthy version of the gene into the body, or you can increase or stabilize the amount of remaining healthy gene through other novel genetic therapies. And this is what people try now.

There are remarkable advances that have been made for 10 to 20 neurological disorders, for example. These are typically rare disorders. But the beautiful thing is that if you look back at the literature and conferences over the last months to two years, for many rare diseases there are already examples where people can try to cure the disease in mice. And they can do it in about 1 in 20 or 30 diseases.

Advertisement

The beauty of these genetic approaches is that the framework is the same, but you only exchange the gene that you want to target. Basically, the vehicle — the approach of how this medicine works — is similar and you can exchange it. It’s the same underlying premise of the mRNA vaccines that we use to immunize ourselves against the coronavirus…. The same underlying premise or idea is also behind the targeted therapies for neurological diseases.… So that makes many people very hopeful that this will translate to human success as well.

Related Articles

DNA
February 6, 2024
Is the MTHFR Gene Mutation Associated With Thrombosis?

The relationship between MTHFR variants and thrombosis risk is a complex issue, but current evidence points to no association between the most common variants and an elevated risk

HVI_Kelley_4277155_Patient Procedure Shoot- First in Human Trial
October 27, 2023
Cleveland Clinic Treats First Patient With Investigational Gene Therapy for Hypertrophic Cardiomyopathy

One-time infusion of adenovirus-based therapy is designed to restore heart muscle function

23-NEU-4035612-CQD-Hero-650×450
August 17, 2023
Parkinson’s Disease Research in Women (Podcast)

Studying gender-specific health factors promises new insight into diagnosis, prognosis, treatment

23-NEU-3989309-CQD-Hero-Podcast-650×450 (1)
July 3, 2023
Genetics of Parkinson’s Disease in Latino Populations (Podcast)

Consortium is uncovering risk factors that spur disease development in an understudied group

23-CCC-3620671-CQD-650×450-1
February 22, 2023
Determining Autism, Cancer Risk in Patients with PTEN Hamartoma Tumor Syndrome

Cleveland Clinic researchers receive $2 million grant from the National Institutes of Health

22-NEU-2638258 genetics_650x450
August 8, 2022
The Case for a Precision Medicine Approach to Training Epilepsy Clinicians

New Cleveland Clinic fellowship fosters expertise in the genetics of epilepsy

21-URL-2361635 CQD 650×450
June 23, 2022
Managing Refractory Hypocalcemia in an Asymptomatic Patient During Pregnancy

Renal genetic testing confirms diagnosis, guides management

22-NEU-2832861-epilepsy-evaluation-in-infant-650×450
April 6, 2022
Prediction Model Aids in the Early Diagnosis of Dravet Syndrome

Integrates genetic and clinical data to distinguish from GEFS+ and milder epilepsies

Ad