• Profile

Xin Tang is an Assistant Professor of Neurosurgery at Boston Children’s Hospital and Harvard Medical School. He earned his PhD in Neurobiology from Pennsylvania State University and completed his postdoctoral research at the Whitehead Institute for Biomedical Research at MIT. His scientific interests primarily focus on understanding the molecular and cellular basis of pediatric brain diseases to ultimately develop therapeutic methods that can be applied clinically and improve patient care.

Additionally, he received the Simons Foundation Autism Research Initiative Award, served as the chief editor of the book “Neuronal Chloride Transporters in Health and Disease,” and authored “Genome Editing: Applications for Disease Modeling and Cell Therapy.”

• Question A: Can you briefly introduce your research field to those outside the industry in one sentence?

Xin Tang: Our research field is drug development for brain diseases, utilizing stem cells, gene editing, and genetic engineering technologies to establish models of human brain diseases. We use these models to understand the mechanisms of diseases, which serves as a basis for targeted drug discovery.

• Question B: Could you provide a simple explanation of the treatments for children’s brain diseases? In these treatments, what role does gene therapy play?

Xin Tang: Pediatric brain diseases are diverse, with a significant portion being neurodevelopmental disorders, which are diseases of the brain that occur during its development, distinct from neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Degenerative diseases may result from a variety of environmental factors over a lifetime, such as diet, sleep, stress. However, neurodevelopmental disorders are mainly genetic and typically occur within the first few years of life, with environmental factors playing a smaller role. These are mainly due to mutations in a single gene or interactions among several genes.

Pediatric neurological diseases cover a wide range, including autism, ADHD, schizophrenia, depression, and more. Compared to many other diseases, there are relatively fewer drugs and treatment options for brain diseases because: firstly, it’s difficult to deliver drugs to the brain, and secondly, the brain’s complexity is extremely high, different from organs like the liver or kidneys. Hence, for neurological diseases, sometimes medication is used to alleviate symptoms, and for more severe conditions like epilepsy and brain tumors, very precise neurosurgery is required. The child’s brain is still growing and is a very fragile organ. So, in general, the treatments we can offer are significantly insufficient, leaving a large unmet medical need.

In the United States, the latest statistics show that about one in six children will have a neurodevelopmental disorder, indicating a high incidence rate covering a broad population. These disorders come in various forms and degrees of severity. More severe cases can lead to cerebral palsy, brain malformations, and developmental deficiencies, among other structural issues. Milder forms manifest problems in the connections between neurons or in gene expression.

To date, treatment options for neurodevelopmental disorders are very limited. Gene therapy, although it holds the possibility of curing with a single treatment, still faces significant technical obstacles in the treatment of neurological diseases. A primary challenge is how to deliver gene therapy into the brain and cover enough brain tissue. The brain contains various cell types, and targeting the disease-related cell types to eliminate the problems caused by pathogenic genes in those cells poses significant difficulties at every step. Gene therapy has made rapid progress in the past decade. However, to date, gene therapy has not yet reached the clinical stage where it can accurately target and modify the relevant genes to treat diseases.

• Question C: What is the ultimate goal for your field? What contributions have you made in this field?

Xin Tang: The ultimate goal, in a nutshell, is to completely cure brain diseases. Let’s break down this goal: In most cases, neurodevelopmental diseases in children are problems caused by genetic mutations during brain development. These mutations might be carried from the fertilized egg, but because children generally do not interact much with the outside world in their first few years, symptoms of autism are hard to detect and usually are not identified and diagnosed until around the age of two or three.

The question of whether using drugs or gene therapy after the age of three or later can truly eradicate the cause of the disease, and whether it can make up for lost time, is very important. Since the brain is continuously developing, whether it can recover after missing the critical period of brain development is a controversial issue. A traditional view holds that brain development has a very short critical period, during which neurons develop, neural connections are formed, and various basic functions are established. So once development is affected by brain diseases, missing this period means there’s no chance of recovery.

Research in the last decade, particularly with genetically engineered mouse models of disease, suggests that neurodevelopmental disorders are not irreversible. Repairing genetic mutations in adulthood can, to some extent, remove the cause of the disease and improve the condition. If we compare the entire brain to a guitar, the brains of children with autism or other developmental diseases are not like a smashed guitar but rather one that is not tuned accurately. Therefore, by finding the right place to adjust the tuning, it may be possible to restore basic functions. A decade ago, this was just a hypothesis, but now it has gradually become a consensus. Researchers have seen enough diseases that have viable methods to achieve recovery in mice or other preclinical models, so it’s starting to be considered feasible.

Moreover, early diagnosis is also very important, and in recent years, it has become possible due to cheaper genetic sequencing and many sequencing diagnostics being covered by insurance. They can effectively diagnose neurodevelopmental diseases. Once a genetic mutation is found, we can know which diseases it is associated with, greatly increasing the accuracy of diagnosis.

Secondly, the extent to which this genetic mutation will affect the child’s development, what kind of intervention or treatment he might need at what age, and what effects might be produced, can all start to be better predicted. Currently, we have compiled a large database for various diseases, their subtypes, and the subsequent development patterns and required therapies for each disease. Through such genetic diagnostics, patients’ families can also organize, forming foundations or support groups to exchange experiences, pool resources for fundraising, or support relevant research institutions. In summary, in the last five to ten years, this trend has become increasingly apparent: earlier and more accurate diagnosis and treatment.

• Question D: Would the related gene therapy bring about some ethical issues?

Xin Tang: In most cases, gene therapy does not refer to treatment at the embryonic stage but to somatic cell therapy. The difference between the two is that embryonic therapy, for example, involves modifying the genes of sperm, eggs, or fertilized eggs from the beginning, thereby transforming every cell in your body, including germ cells, to carry the modified trace. This is called germ cell gene editing. Another type is somatic cell gene editing, for example, if a patient has a brain disease, this mutation may be present throughout the body, and we use gene editing to target and treat the disease specifically. We only need to change a very small part of the mutated gene in a certain organ, and we do not touch the rest of the cells in the body. When the related technology becomes more mature, we can also correct some genes in the brain, which is a completely different concept from germ cell editing.

Somatic cell editing will only change this one patient and cannot be passed on to the next generation. However, germ cell editing will lead to such a result because the editing will exist in all cells of that person at all stages of growth and will also affect all of their offspring. Thus, this is not just a medical issue but can even be considered a public health issue, as the results of germ cell gene editing will produce intergenerational inheritance. This is a very complex social issue and is likely to exacerbate social inequality.

For example, if a certain gene causes a child to die before the age of three, we should definitely change this gene if we have the capability. But what if the gene only makes the child short? Should we change it then? What if it’s just about wanting the child to be physically strong? Or wanting the child to have red hair, or to increase the chances of getting into college? This is clearly overstepping boundaries. Therefore, where to draw the line in these matters is also a very worthwhile question to discuss.

• Question E: In recent years, artificial intelligence, which has become very popular, is there any possibility that it could assist in the treatment of children’s brain diseases in some aspects?

Xin Tang: Certainly, artificial intelligence is a versatile technology that can be utilized in many areas, including the classification of various brain diseases. For example, autism is a broad category that includes distinctions in severity and causes. AI technology can play a significant role in differentiating disease subtypes, such as genotypes and phenotypes. In these analyses, big data can be employed, combined with population studies, to develop frameworks for analysis.

Currently, these frameworks exist primarily within the experience and diagnosis of doctors. Doctors are experienced and highly skilled but typically specialize in only one specific area and cannot diagnose all types of diseases. Even for some less common disease types, experienced doctors might encounter them for the first time outside of textbooks. However, artificial intelligence has the potential to achieve a level of expertise and versatility that covers a wide range of diseases. Given the vast number of disease subtypes, it is impossible for every hospital to have experts in all areas. Therefore, using artificial intelligence for preliminary diagnoses and classification, and then directing patients to specialists in the relevant fields at specific hospitals, can bring tangible convenience to patients.

• Question F: What are the specific characteristics of children’s brain diseases compared to those of adults?

Generally speaking, the treatment of diseases in children, compared to adults, has higher requirements because children’s bodies are smaller, their physique is relatively weaker, and their brains are still in the development stage. Therefore, when using any kind of medication, one must not only consider its therapeutic effect but also its side effects. The safety standards for developing medication protocols for children are much higher. Moreover, the medication for brain diseases differs from that for tumors; tumor medications may only need to suppress the tumor within one or a few treatment courses, but many medications for brain diseases need to be taken over a long period. This further increases the requirements for medication safety, ensuring that for children with different physiques, the side effects are not too strong. Therefore, how to reduce side effects, how to deliver medications into the brain, and how to accurately treat are all requirements that need to be met during drug development.