SYnAbs innovative monoclonal antibodies targeting hemoglobinopathia diseases

A short introduction to Hemoglobinopathia


Hemoglobinopathia are diseases associated with a genetic abnormality of hemoglobin, blood protein used to transport oxygen. Hemoglobin is found basically inside red blood cells (erythrocytes), which gives them their red color.


Human hemoglobin consists of four identical chains :

  • two α (alpha) chains
  • two β (beta) chains

Each of these channels is associated with a prosthetic grouping called heme. The name of hemoglobin comes from two words: heme and globin, symbolized by "Hb".


The alpha and beta genes of globin are coded respectively on the chromosomes 16 and 11. But like many proteins, chains hemoglobin present various mutations that have the most often no impact clinical. These diseases are autosomal recessive Mendelian transmission, meaning that the disease appears only in children whose both parents are carriers of the anomaly, it is the homozygous form. In the heterozygous form (only one affected parent), the disease is most often silent, remaining transmissible.


More than 500 hemoglobins abnormal have been listed and they fall into two broad categories.


Sickle cell disease monoclonals


Also called hemoglobinosis S, sicklemia or cell anemia falciformes, Sickle cell disease is a hereditary disease, autosomal recessive, which is characterized by an alteration of hemoglobin. The red blood cells of homozygous individuals, HbS / S, do not practically only contain HbS. These molecules have the property of polymerizing when deoxygenated, giving rise to training of fibers that deform the globule and give it an appearance in sickle.


More than 50 million people worldwide are affected by the Sickle cell disease, and more than 250'000 children with a serious form are born each year with the genetic anomaly. Sub-Saharan Africa, Middle East, India, Brazil are the main locations of Sickle cell disease.


Manifestations of the disease are multiple and can be listed as

  • "Vaso-occlusive" crises, caused by the obstruction of capillaries
  • Acute pain episodes due to vaso-occlusive seizures
  • Hand-foot or dactylitis syndrome
  • Hemolytic anemia
  • Acute chest syndrome
  • Stroke, Cerebrovascular accident
  • Increased susceptibility to infections
  • Chronic complications (Heart attack, kidney, dermatological, PAH, Retinopathy, Priapism, cholelithiasis…)

So far, there is no cure for this genetic disease, except hematopoietic stem cell transplantation. The diagnosis is currently made:

  • by examining the shape of the red cells,
  • by analyzing hemoglobin by electrophoresis
  • by genetic testing.

SYnAbs has consequently developed pair of monoclonal antibodies against different confidential types of Sickle cells diseases, to produce sandwich ELISA assay. Thanks to its unique expertise, coupled with rat monoclonal antibodies technologies, SYnAbs was able to target specific mutations on hemoglobin and generate immune response against very specific parts of these poor immunogenic antigens.


SYnAbs has now at your disposal off-the-shelf highly specific anti-HbA, anti-HbC, anti-HbE, anti-HbS and anti-panHb monoclonal antibodies.


Thalassemia monoclonals


Thalassemia are hereditary diseases, autosomal recessive are characterized by a lack of production hemoglobin :

  • Beta-thalassemia
  • Alpha-thalassemia

Beta-thalassemia affects mainly people from Mediterranean region, the Middle East, Asia (China, India, Vietnam, Thailand) and Black Africa. It reaches as many women than men. Around 200.000 people suffer from beta-thalassemia worldwide. Adult hemoglobinopathy testing market is growing by 3,9% (CAGR) and thalassemia market is estimated to reach 3,53$ billion by 2022.


According to the fact that the production of beta chains of globin is absent or only reduced, we distinguish:

  • ß-thalassemia major (Cooley anemia)
  • Intermediate ß-thalassemia
  • ß-thalassemia minor

ß-thalassemia major (Cooley anemia)


The first signs of ß-thalassemia major appear only after the age of 6 months because the newborn's blood still contains a lot of fetal hemoglobin HbF (alpha2 / gamma2), under a often very heterogeneous form according to individuals:

  • Severe hemolytic anemia
  • Fewer
  • Irritability
  • Hepatomegaly
  • Splenomegaly
  • Ictery
  • Developmental delay

To compensate for massive hemolysis, erythropoiesis is increased in bones leading to bone deformities. In the child the facial bones get thicker (deformation of the jaws,

flattening of the root of the nose, excessive spacing of the eyes).


Secondary complications due to iron overload following hemolysis / continuous transfusion may appear :

  • Endocrine and metabolic abnormalities
  • Hypogonadism 40-55%
  • Growth retardation 33%
  • Diabetes 6-13%
  • Hypothyroidism 10%
  • Heart complications
  • Cardiac insufficiency (hemosiderosis)
  • Arrhythmias
  • Cholelithiasis 

The diagnosis is currently performed :

  • Clinical suspicion (signs, symptoms, origin ...)
  • Blood smear (hypochromic anemia, microcytic)
  • Biochemistry: Hemolysis (free biliary, LDH, Haptoglobin)
  • Serum iron, ferritin
  • Electrophoresis of hemoglobin (HbA2 3.5-8% HbF 1-2%) 

Treatments are composed of :

o Blood transfusion

o Folic acid

o Iron Chelator


Intermediate ß-thalassemia


In intermediate beta-thalassemia, both beta genes are altered, but they still allow the manufacture hemoglobin in a reduced amount. The symptoms are therefore much less important than in Cooley anemia :


o Hypochromic microcytic anemia

o Bone abnormalities (+/-)

o No stunting


ß-thalassemia minor


Beta-thalassemia minor is due to mutation of only one of the two beta genes.


Generally, this form does not have consequence on health, since the other gene is able to compensate for the anomaly and make enough beta chains for produce a normal hemoglobin level or close to normal.




Alpha-thalassemia is very common. It mainly affects populations from Asia (Cambodia, Laos, Burma, Thailand in particular), in its intermediate or serious forms, from Africa equatorial, and the Mediterranean basin in its minor forms. Alpha-thalassemias occurs on chromosome 16, 2 genes, encode for the alpha strings of the globin.


The diagnosis is currently performed by:

  • Blood smear
  • Electrophoresis of hemoglobin