For many people their awareness of Amyotrophic Lateral Sclerosis (ALS), often referred to as "motor neuron disease" or Lou Gehrig’s disease, is limited to the Ice Bucket Challenge or to the visible signs of the disease on high profile people such as Professor Stephen Hawking in the UK, health care advocate Ady Barkan in the U.S., or businessman Cai Lei in China, former Vice President of JD.com and an advocate for ALS research and development.

ALS is a terrifying progressive neurodegenerative disease that affects motor neurons and gradually paralyzes people as the brain is unable to communicate with the muscles in the body. As the disease progresses, patients often find themselves in a conscious state, yet progressively unable to move, speak, swallow, and eventually unable to breathe. As the condition worsens, many rely on the aid of computer programs that track eye movements and then produce a synthetic voice to be able to communicate. 

While considered to be a rare disease, there are estimated to be more than 200,000 people living with ALS globally, with the number increasing. Some ALS cases are inherited, but many more are sporadic and can affect anyone regardless of age, ethnicity or gender. 

There are currently no medical treatments that can cure ALS. The disease is also complex as there does not appear to be one thing that causes it, and there may be multiple interacting causes particularly in terms of people’s genes.

Dr. Jin Xin, Chief Scientist and Director of the Institute of Precision Health Research at BGI-Research, explains that some genes have already been clearly identified in relation to ALS. Moreover, these specific genetic mutations have been shown to significantly increase the likelihood of developing the disease. Current studies show that, among the more than 40 genes associated with the onset of ALS, 5-10% are related to hereditary factors, of which 50-70% are well-defined. However, each patient's circumstances vary. The occurrence of ALS could be due to many factors, including recessive and dominant genetic patterns, as well as spontaneous mutations.

Advances in genomics and single cell technology offer some hope as scientists seek to understand ALS better. BGI’s cutting-edge spatial omics technology, Stereo-seq, provides a nanoscale resolution with a broad range of vision enabling 25,000 genes to be detected simultaneously as well as determining the type and location of cells relative to one another to be able to see how they interact with each other over time. By revealing the inner workings of genes and how they mutate over time, scientists can take a precision focus in examining their specific role in the formation of ALS. 

The challenge for scientists is that it is not always the same genes or combination of genes that causes ALS or other rare diseases, and it is only by examining the genome of multiple ALS patients that scientists can begin to understand the causes of gene mutations associated with ALS.

To this end, Dr. Yin Ye, CEO of BGI Group, in collaboration with Mr. Cai Lei, launched in early 2023 a free gene testing and data analysis program for patients with ALS. 

The project received a total of 194 samples, and ultimately BGI sequenced and analyzed 184 samples from 74 family lineages. The results found about six times as many suspected loci as traditional detection methods. 

Due to the small sample size in previous studies, the scientific community believed that the onset of ALS might be a random event, with only 5-10% of ALS cases related to genetic changes or mutations. However, BGI has made a breakthrough in this understanding, enabling further identification of the genetic characteristics of the ALS patient population in China and providing clues for identifying new genetic targets. 

To take this research to the next stage, in October 2023, Dr. Yin announced that he and Mr. Cai would provide free whole genome sequencing testing for 200 family lineages. To support this, BGI will also provide its latest blood collection technology. Compared to the current saliva sample collection, it is not only more convenient, but also provides more precise results.

Ultimately, this work when combined with other scientific research being undertaken around the world, will help scientists to understand ALS better, bring hope to the families where ALS is present, and make the possibility of finding a cure for ALS a greater reality.

Reflecting on this work and the hope it brings for the future, Dr. Yin said, "Perhaps what we haven't been able to accomplish in the past, we will surely achieve in the future. If there are more people like Mr. Cai, a fighter for ALS treatments, I believe the day when we conquer ALS will come much sooner. We are making the hope bigger and the waiting time shorter."