Gene Therapy and FTD

Gene Therapy, and related approaches like gene modification, are promising strategies to treat FTD. Gene therapies have successfully treated other genetic conditions, offering hope for people living with genetic forms of FTD, and perhaps those with sporadic FTD as well. But what is gene therapy, and how does it work?

Our DNA holds the instructions that tell our body how to grow and function. Each gene acts like a recipe to make a protein. When a gene is changed, that change, or “variant,” can lead to a disorder, like FTD. Gene therapy is a broad term, encompassing several methods of delivering into the body a version of a gene that can make a functional protein. The hope is that gene therapy can slow or stop the progression of disorders like FTD. The earlier symptoms are detected, the more likely it is that gene therapy will be effective. (For more information on genes and genetics, visit the National Institute of General Medical Sciences.)

In FTD, gene therapy needs to be delivered to the brain, which is challenging; our brains are very good at protecting themselves. Gene therapy is delivered using microscopic particles known as “vectors.” Different vectors are used depending on the amount of genetic information being delivered.

One common form is an adeno-associated vector, or AAV. AAVs are technically viruses and are therefore naturally able to deliver genetic material to a cell. AAVs used in gene therapy have had their own viral (and harmful) DNA replaced with therapeutic genetic material. Ideally, AAVs deliver the corrected genetic material to the relevant cells in a one-time treatment with long-term benefits.

Another way to fix a harmful genetic variant is by administering an antisense oligonucleotide, or ASO. An ASO can either block a faulty protein from being made or increase production of a functioning protein. Because ASOs do not integrate into a cell’s genetic signature, this treatment is unlikely to be permanent, and therapeutic effects may require repeated treatments.

There are several ways to safely and effectively administer gene therapy. AAVs or ASOs can be given as an injection into the bloodstream (intravenous), into the cerebral spinal fluid through a lumbar puncture (intrathecal), or directly into regions of the brain (intracisternal, intrathalamic). Scientists have decades of experience safely completing the various procedures. To learn more about delivery of gene therapy, visit the American Society for Gene and Cell Therapy’s patient education center and the National Human Genome Research Institute.

The American Society of Gene + Cell Therapy

To learn more about what to expect from gene therapy, including potential risks, visit the Mayo Clinic’s gene therapy overview.

Many clinical trials for potential FTD treatments focus on genetic forms of FTD. If a genetic variant leads to the production of toxic proteins or the loss of a functioning protein, scientists can design treatments to correct the specific problem. When scientists understand the effect of a specific genetic variant, researchers have a better understanding of the disrupted processes and can target treatments that correct them. Eventually, information learned by treating genetic FTD may be applied to sporadic FTD and other neurodegenerative disorders.

If you have a genetic form of FTD, AFTD encourages you to consider if participating in a clinical trial for FTD gene therapy is right for you or your relative. To learn more about available clinical trial options, enroll in the FTD Disorders Registry, visit ClinicalTrials.gov, or contact AFTD’s HelpLine at 866-507-7222 or info@theaftd.org.