Gene Therapy for Neurological Disorders

Question 1

Name some advantages to intraparenchymal delivery?

Answer 1

Bypass BBB and delivers genes directly to brain region and neurons of interest.
One and done based gene therapy.
Well tolerated in clinicals trials to date.
Minimal biodistribution to peripheral organs.
Reduced immunogenicity.
Significantly lower vector doses required comapred to other toures of administration.

Question 2

Where does intrathecal injection enter the body?

Answer 2

access via spinal cord CSF via the space under the arachnoid membrane

Question 3

Where does the intracerebroventricular injection enter the body?

Answer 3

into the CSF via the lateral ceerebral ventricles

Question 4

Where does the intracisternal injection enter the body?

Answer 4

into the CSF via the cerebromedullary cistern

Question 5

What are some disadvantages to IV administration?

Answer 5

IV injection exposes the virus to potential antibody neutrilization in subjects who have been previously exposed to natural AAV infections
IV admin requires highter total doses to achieve efficient transduction than other routes
Iv admin results in broad and substantial vector disturbtion to multiple peripheral tissues and organs - associated biological impact of the potential for immune response against the capsid.

Question 6

Name the three rate-limiting enzymes in the dopamine synthesis pathway

Answer 6

GTP cyclohydrolase 1 (GCH1), tyrosine hydoxylase (TH) and aromatic amino acid DOPA decarboxylase (AADC)

Question 7

Which new gene therapy has been used to treat spinal muscle atrophy?

Answer 7

AVXS-101

Question 8

Name some PD gene therapy which are being trialed.

Answer 8

1, AAV2-NRTN
2. AAV2-GDNF
3. LRRK2 ASO
4. AAV-GBA1

Question 9

How are AAV2-GDNF and AAV-GBA1 delivered?

Answer 9

IPa injections

Question 10

What gene therapy has been trailed for huntingtons disease?

Answer 10

AMT-130

Question 11

What gene therapy has been trailed for ALS?

Answer 11

AAV9-SOD1