Curing Disease Through Technology

There have been many technological advances in medicine in the past decade. Many of these resulted in better ways to diagnose and treat diseases, but rarely has technology advanced to actually cure a disease. Recent developments in gene therapy seem to have resulted in reports of actually curing a major disease that affects millions of people here at home and around the world — sickle cell disease. 

Sickle cell disease is an inherited hematological disorder resulting from the amino acid, valine, being inserted into the β-globin chain of the normal hemoglobin unit in place of the normal amino acid, glutamic acid. It was first described in 1910 by Dr. J.B. Herrick and was the first disease for which a genetic mutation was identified.^1,2 This gene mutation causes red blood cells to become rigid and assume an abnormal shape (the sickle shape) after giving up the oxygen molecule the hemoglobin is carrying. Because of this, and other problems that occur at the molecular level, the red blood cells occlude small blood vessels and capillaries, causing ischemia of the affected organ or tissue. It is usually when this occurs in the lower extremity of a patient and an ulcer develops that we, as wound care professionals, become involved with sickle cell disease. 

Sickle cell ulcers are most likely to develop in men with the homozygous form of sickle cell disease.³ Up to 75% of patients older than 30 years of age will have a sickle cell ulcer, which most frequently occurs on the medial malleolar area of the ankle.^4,5 In the United States, there are more than 80 000 patients with sickle cell disease, making the incidence of sickle cell ulcers underreported and underappreciated.⁶ 

Treatment of these sickle cell ulcers has been difficult and unreliable due to the underlying cause (sickle cell disease) not having a curative treatment. With advances in stem cell therapy and gene technology, this is changing. In 2007, Bernaudin and his colleagues⁷ found that stem cell transplantation from a relative without sickle cell disease had resulted in a correction of the abnormal hemoglobin production over a period of time; their⁷ work was further confirmed by a report in 2017.⁸ These patients underwent a standard stem cell transplantation procedure with ablation of their bone marrow and replacing it with normal marrow from a donor.⁸ Unfortunately, there was significant resistance in using this procedure on patients with sickle cell ulcers because of the potential for life-threatening infection developing when the patient had to be immunosuppressed. Fortunately, Connor et al⁹ had the courage to perform the procedure in a patient with a sickle cell ulcer and found that the ulcer did not cause any problem — not only was the sickle cell disease cured, but also the ulcer healed.

Even more exciting has been the recent report from the National Institutes of Health¹⁰ in which 6 patients treated with gene therapy of their own cells successfully were cured of their disease. Some of the patient’s own bone marrow was treated with a lentivirus containing the gene for the normal hemoglobin. The virus then inserted this normal gene into the patient’s cells, which were given back to the patient. At 3 months posttreatment, all 6 of the patients had normal hemoglobin-containing cells in their circulation.¹⁰ This innovation will allow sickle cell patients with and without ulcers to be treated without the risk of stem cell transplantation. 

These advances in technology offer the possibility of patients being cured of sickle cell disease and not having to worry about developing a sickle cell ulcer — or any of the numerous complications of this disease. Hopefully, our discussion of sickle cell ulcers will be of historical interest only in the near future.

Terry Treadwell, MD, FACS
woundseditor@hmpglobal.com