Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives.

Gene therapy is defined as the administration of genetic material to modify, manipulate gene expression or alter the properties of living cells for therapeutic purposes. Recent advances and improvements in this field have led to many breakthroughs in the treatment of various diseases. As a result, there has been an increasing interest in the use of these therapies to treat motor neuron diseases (MNDs), for which many potential molecular targets have been discovered. MNDs are neurodegenerative disorders that, in their most severe forms, can lead to respiratory failure and death, for instance, spinal muscular atrophy (SMA) or amyotrophic lateral sclerosis (ALS). Despite the fact that SMA has been known for many years, it is still one of the most common genetic diseases causing infant mortality. The introduction of drugs based on ASOs-nusinersen; small molecules-risdiplam; and replacement therapy (GRT)-Zolgensma has shown a significant improvement in both event-free survival and the quality of life of patients after using these therapies in the available trial results. Although there is still no drug that would effectively alleviate the course of the disease in ALS, the experience gained from SMA gene therapy gives hope for a positive outcome of the efforts to produce an effective and safe drug. The aim of this review is to present current progress and prospects for the use of gene therapy in the treatment of both SMA and ALS.

Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia.

Recent years have brought significant progress in the treatment of B-cell acute lymphoblastic leukemia (ALL). This was influenced by both the improved schemes of conventionally used therapy, as well as the development of new forms of treatment. As a consequence, 5-year survival rates have increased and now exceed 90% in pediatric patients. For this reason, it would seem that everything has already been explored in the context of ALL. However, delving into its pathogenesis at the molecular level shows that there are many variations that still need to be analyzed in more detail. One of them is aneuploidy, which is among the most common genetic changes in B-cell ALL. It includes both hyperdiploidy and hypodiploidy. Knowledge of the genetic background is important already at the time of diagnosis, because the first of these forms of aneuploidy is characterized by a good prognosis, in contrast to the second, which is in favor of an unfavorable course. In our work, we will focus on summarizing the current state of knowledge on aneuploidy, along with an indication of all the consequences that may be correlated with it in the context of the treatment of patients with B-cell ALL.

Insights into Modern Therapeutic Approaches in Pediatric Acute Leukemias.

Pediatric cancers predominantly constitute lymphomas and leukemias. Recently, our knowledge and awareness about genetic diversities, and their consequences in these diseases, have greatly expanded. Modern solutions are focused on mobilizing and impacting a patient's immune system. Strategies to stimulate the immune system, to prime an antitumor response, are of intense interest. Amid those types of therapies are chimeric antigen receptor T (CAR-T) cells, bispecific antibodies, and antibody-drug conjugates (ADC), which have already been approved in the treatment of acute lymphoblastic leukemia (ALL)/acute myeloid leukemia (AML). In addition, immune checkpoint inhibitors (ICIs), the pattern recognition receptors (PRRs), i.e., NOD-like receptors (NLRs), Toll-like receptors (TLRs), and several kinds of therapy antibodies are well on their way to showing significant benefits for patients with these diseases. This review summarizes the current knowledge of modern methods used in selected pediatric malignancies and presents therapies that may hold promise for the future.

The New Treatment Methods for Non-Hodgkin Lymphoma in Pediatric Patients.

One of the most common cancer malignancies is non-Hodgkin lymphoma, whose incidence is nearly 3% of all 36 cancers combined. It is the fourth highest cancer occurrence in children and accounts for 7% of cancers in patients under 20 years of age. Today, the survivability of individuals diagnosed with non-Hodgkin lymphoma varies by about 70%. Chemotherapy, radiation, stem cell transplantation, and immunotherapy have been the main methods of treatment, which have improved outcomes for many oncological patients. However, there is still the need for creation of novel medications for those who are treatment resistant. Additionally, more effective drugs are necessary. This review gathers the latest findings on non-Hodgkin lymphoma treatment options for pediatric patients. Attention will be focused on the most prominent therapies such as monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T cell therapy and others.