Treatments being developed

Small molecule treatments

Small molecules are chemical compound that are under a certain size (a molecular weight of <900 Da). Most medicines in routine use are small molecules, for example, aspirin, penicillin and insulin. 

Small molecule drugs treat health conditions by interacting with proteins within the body. Because of their small size, small molecule drugs can pass into cells to reach their targets inside the cell. This video explains more about small molecule medicines and how they work. 

Several small molecule treatments are being investigated for the treatment of SCN2A-related conditions. To reduce seizure frequency, these may target:

  • Sodium channels
  • Neurotransmitters.

Advanced therapeutics

Advanced therapeutics are innovative therapies. They include gene, cell and tissue-based therapies. These types of therapies are relatively new and are only being used in a small number of health conditions.

In SCN2A-related conditions, advanced therapeutics could be used to:

  • Turn the SCN2A gene ‘up’, so that more Nav1.2 channels are made. 
  • Turn the SCN2A gene ‘down’, so fewer Nav1.2 channels are made. 
  • Tell the SCN2A gene to make a full-size Nav1.2 channel, instead of a shortened version.

Antisense oligonucleotides (ASOs)

An ASO is a type of chemical known as a nucleotide. DNA is also a nucleotide. ASOs are being investigated to treat gain of function and loss of function changes in the SCN2A gene. 

How ASOs work in SCN2A gain of function variants

ASO’s are sent into neurons

The ASOs pair with the ‘messenger” that tells theneurons to make the Nav1.2 channel

With fewer active messengers in the neurons, less Nav1.2 channels are made

With fewer sodium channels, neurons are less excitable and send fewer messages

CRISPR activation

CRISPR-Cas9 is a new genetic technology that can be used to edit (change) the genetic code. It can also be used to turn genes up or down. 

A form of CRISPR-Cas9 called CRISPR activation (CRISPRa) is being investigated as a way of ‘turning up’ the working SCN2A gene in individuals with loss of function changes in SCN2A. Unlike regular CRISPR-Cas9, CRISPRa does not edit (change) the genetic code.

How CRISPRa works in SCN2A loss of function variants

A virus is sent into neurons. The harmful effects of the virus are turned off before it is used

The virus carries:

A ‘guide’ that matches part of the SCN2A gene.

A protein called Cas9 (dCas9), attached to an ‘activator’

The guide directs dCas9 and the activator to a specific region at the start of the SCN2A gene

The activator tells the cells to turn on the working SCN2A gene

the cell makes more Nav1.2 sodium channels, and more messages are sent by the neurons