Lamb-Shaffer Syndrome (LAMSHF) was “discovered” in 2012 by Lamb, Shaffer and colleagues. They found that the loss of one of the two SOX5 genes causes a global developmental delay and intellectual disability. We have since discovered that there are a variety of ways the SOX5 gene can be affected (deletion, partial deletion or mutation) and all of them affect the person by inactivating the copy of that gene. This makes it so the person only makes half of the functional SOX5 protein that is needed to function “typically.”
Over the years the research team at the Children's Hospital of Philadelphia has been able to discover what the SOX5 protein is used for (most notably, to form functional cartilage cells during skeleton development), but there is certainly more that they have yet to understand. They know that in order for a person to be typically developing, they need two functional copies of the SOX5 gene, but more research is needed to identify which brain cells rely on that SOX5 protein and to propose appropriate treatment options.
Their current goal is to find safe and effective treatment options for those affected by Lamb-Shaffer Syndrome.
Treatments will be considered safe if they do not cause any new issues.
Treatments will be considered efficient if they can correct the brain defects caused by Lamb-Shaffer Syndrome.
In order to do that, they will begin by unraveling the, still largely unknown, brain defects that are caused by LAMSHF. After that, they will partner with drug experts and clinicians to identify and test candidate drugs. In parallel, they will work on a second project in collaboration with experts at the Children’s Hospital of Philadelphia (CHOP) in order to find a way to potentially fix the gene abnormality in patients with Lamb-Shaffer Syndrome.
Identifying genetic strategies to correct or compensate for disease-causing gene alterations is a dream that world leader researchers at CHOP have already accomplished for several other diseases/syndromes. Now, it's time for them to apply these strategies on Lamb-Shaffer Syndrome. If successful, gene therapy could provide a potential cure (in this instance, a “cure” would mean fixing the gene abnormality) for Lamb-Shaffer Syndrome, but we are still a few years from having everything we need. Technology to correct brain diseases is still in development, but their goal is to contribute as best as possible. Several outcomes are possible: they could correct mutations, they could stimulate the activity of the intact SOX5 copy, or they could add a new copy of SOX5. This project is undoubtedly ambitious and challenging, but the tremendous progress that has been made in this field in the last few years is very motivating and exciting!
The reality is that no one knows what these treatments or “cures'' will look like for those affected by LAMSHF. Neither one will be a magic switch that miraculously takes away all of the symptoms of LAMSHF, but the theory is that it will make the gene work more effectively, thus making it easier for the brain to function properly.
Currently, the research activities rely almost entirely on funding from external sources. To obtain federal funding (NIH grant), the research team need to provide data demonstrating not only their expertise and commitment, but also the feasibility of our proposed project. They have already obtained lots of encouraging data and will continue on that path. A major NIH grant would allow two to three people in the lab to work on the project for up to five years. Once an NIH grant is secured, funding from donations or foundations would still be welcome to boost the efforts, but would no longer be critical. We have been extremely blessed to receive generous support from many family members and friends of patients with Lamb-Shaffer Syndrome over the years. We are immensely thankful to all of you. Your dedication to helping your loved ones has boosted our enthusiasm for research. The donations have allowed the research team to start this project from scratch and reach a point today where they are confident that they will soon be able to provide treatments or potential cures to those with Lamb-Shaffer Syndrome.
Below are the research articles that have been published from various sources regarding the SOX5 gene and Lamb-Shaffer Syndrome: